Electrical devices with enhanced electrochemical activity and manufacturing methods thereof

ABSTRACT

In some aspects, a device is provided having a member with a region of enhanced electrochemical activity. In one aspect, a sensor of enhanced electrochemical activity is provided for detecting an analyte concentration level in a bio-fluid sample. The sensor may include a sensor member of a semiconductor material wherein the sensor member has a surface region of enhanced electrochemical activity. In other aspects, the member may be made of semiconducting foam having a surface region of enhanced electrochemical activity. In some embodiments, the region may be thermally-induced. Manufacturing methods and apparatus are also provided, as are numerous other aspects.

RELATED APPLICATIONS

The present application claims priority to U.S. Provisional PatentApplication No. 61/098,728 filed Sep. 19, 2008, and entitled“ELECTROCHEMICAL DEVICES WITH ENHANCED ELECTROCHEMICAL ACTIVITY ANDMANUFACTURING METHODS THEREOF” which is hereby incorporated herein byreference in its entirety for all purposes.

FIELD OF THE INVENTION

The present invention relates to electrochemical apparatus and methodsof manufacturing thereof.

BACKGROUND OF THE INVENTION

Devices that include electrochemical activity (sometimes referred to aselectrochemical reactivity) find many uses. One use is in the monitoringof an analyte concentration level in a bio-fluid as part of healthdiagnostics. For example, an electrochemical analyte sensor may beemployed for the monitoring of an analyte level (e.g., glucose level) ina patient's blood. Because conventional electrochemical analyte sensorsmay have relatively low sensitivity, a relatively large bio-fluid samplevolume may be required in order to yield an accurate measurement of ananalyte concentration level.

Another area of devices where electrochemical activity is of interest isin the area of electrochemical conversion devices (e.g., fuel cellsand/or batteries, etc.).

Such conventional electrochemical devices (e.g., analyte sensors, fuelcells, batteries, etc.) may require the use of precious metals and/ormay require wet processing steps, which may add significantly to thecost of manufacturing such devices.

Accordingly, it would be beneficial to provide inexpensiveelectrochemical devices, which may have enhanced properties, such aselectrochemical activity.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a sensor including asensor member of a semiconductor material, the sensor member including asurface region of enhanced electrochemical activity.

In another aspect, the present invention provides an analyte sensor fordetecting an analyte concentration level in a bio-fluid sample. Theanalyte sensor includes a first sensor member comprised of asemiconductor material; a surface region of enhanced electrochemicalactivity formed on the sensor member; and an active region positioned incontact with at least a portion of the surface region of enhancedelectrochemical activity.

In a method aspect, the present invention provides a method ofmanufacturing a sensor including the steps of providing a sensor memberincluding a semiconductor material; and providing a surface region ofenhanced electrochemical activity on the sensor member.

In another method aspect, the present invention provides a method ofmanufacturing an electrochemically active device, including the steps ofproviding a member including a semiconductor material; and applying heatto a surface region of the member to bring about a change in anelectrochemical activity of the surface region.

In another aspect, the present invention provides an electrochemicaldevice. The device includes a member of a porous semiconductor material,the member including a surface region of enhanced electrochemicalactivity.

In yet another aspect, the present invention provides an electrochemicalsensor, including a member of a semiconductor material, the memberincluding a region of enhanced conductivity.

Other features and aspects of the present invention will become morefully apparent from the following detailed description, the appendedclaims, and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top plan view of an exemplary embodiment of an analytesensor provided according to the present invention.

FIG. 2 is an enlarged cross-sectional view of an analyte sensor of FIG.1 taken along section line 2-2.

FIG. 3 is an exploded isometric view of the exemplary embodiment of ananalyte sensor of FIG. 1 according to the present invention showing alid being separated for clarity.

FIG. 4 is a partial frontal view of a testing apparatus receiving anexemplary embodiment of an analyte sensor according to the presentinvention.

FIG. 5 is a partially cross-sectioned top plan view of another exemplaryembodiment of an analyte sensor according to the present invention.

FIG. 6 is an enlarged, partially cross-sectioned top plan view of acoded region of an embodiment of an analyte sensor according to thepresent invention.

FIG. 7 is a partial top plan view illustrating a formation of tracks ona sensor member included within an exemplary embodiment of an analytesensor according to the present invention.

FIGS. 8A-8D are top plan views of other exemplary embodiments of sensormembers for inclusion in analyte sensors according to the presentinvention.

FIG. 9A is a micrograph view at 10,000× magnification of an enhancedelectrochemical activity surface according to the present invention.

FIG. 9B is a micrograph view at 10,000× magnification of an unenhancedsurface for comparative purposes.

FIG. 9C is a micrograph view at 500× magnification of an enhancedelectrochemical activity surface according to the present invention.

FIG. 9D is a micrograph view at 500× magnification of an unenhancedsurface for comparative purposes.

FIG. 10 is a micrograph view of a semiconducting fiber including asurface region of enhanced electrochemical activity surface according tothe present invention.

FIG. 11A is a first plot illustrating an electrochemical response (innA) of an inventive analyte sensor employing a surface region ofenhanced electrochemical activity according to the present invention ascompared to a comparative analyte sensor without an enhanced surfaceregion.

FIG. 11B is a second plot illustrating an electrochemical response (innA) of an inventive analyte sensor employing a surface region ofenhanced electrochemical activity according to the present invention ascompared to a comparative analyte sensor without an enhanced surfaceregion.

FIG. 12 is a flowchart illustrating methods of manufacturing membersincluding a surface region of enhanced electrochemical activity surfaceaccording to the present invention.

FIG. 13 is a perspective view illustrating a porous semiconductor devicehaving a surface region of enhanced electrochemical activity surfaceaccording to the present invention.

FIG. 14 is a cross-sectional side view of an exemplary embodiment of ananalyte sensor provided according to the present invention.

DETAILED DESCRIPTION

According to a first aspect of the present invention, an electrochemicaldevice is provided including a member made, at least in part, of asemiconductor material. A surface portion of the member may include asurface region of enhanced electrochemical activity (hereinafterreferred to as an “enhanced surface region” or an “enhanced region”).“Surface region of enhanced electrochemical activity” as used hereinmeans a surface region having increased electrochemical reactivity, thatis, more rapid oxidation and/or reduction kinetics at a given electricalpotential as compared to an untreated surface region of an article ofthe same size and material.

This region may be formed by the application of heat, i.e., it may bethermally induced. The enhanced surface region may allow for enhancedelectrical current generation in electrochemical sensors and devices,such as in analyte sensors and fuel cells, for example. Further, thisenhancement may simplify construction by reducing or eliminating a needfor precious metals and/or a need for wet processing steps. In someembodiments, the semiconductor material may be silicon carbide. In otherembodiments, the member may include a porous semiconducting material(e.g., porous semiconducting foam).

In some embodiments, the device may be an analyte sensor that mayinclude a sensor member made at least in part of a semiconductormaterial. The sensor member may include a surface region of enhancedelectrochemical activity. An active region (e.g., one or more catalyticagents and/or reagents) may be provided in contact with the enhancedregion. Accordingly, the sensor may be used for analyte detection. Inoperation, the active region may be adapted to react with, and convert,an analyte in a bio-fluid sample into reaction products from which anelectrical current may be generated.

The sensor member may be disposed in another element, such as a base orhollow member (e.g., a needle-like member) wherein the sensor mayoperate as a working electrode of the sensor, for example.Advantageously, providing a surface region of enhanced electrochemicalactivity on the sensor may provide enhanced signal generation ascompared to like articles without the enhanced activity surface.

These and other embodiments of electrochemical devices, sensors, analytesensors, apparatus including the analyte sensors, and methods formanufacturing the devices and sensors are described below with referenceto FIGS. 1-14.

FIGS. 1-3 show various views of an exemplary embodiment of an analytesensor 100 provided according to the present invention. The analytesensor 100 may include a base 110 which may be formed of any suitableinsulating material such as a polymer (e.g., polycarbonate, polystyrene,high density polyethylene, polyethylene terephthalate, polyimide, orlike insulating material). The base 110 may have a first sensor member120 mounted thereon, which may be mounted by including some level ofphysical impression into the base 110. For example, when the base 110 isa deformable polymer sufficient pressure and/or heat may be appliedthereby causing a cladding 124 of first sensor member 120 to impressinto the base 110. Furthermore, the impression may be molded into thebase 110. Optionally, the first sensor member 120 may be adhered orglued, heat fused, ultrasonically fused, or otherwise mounted to thebase 110. In some embodiments, the first sensor member 120 may bemounted to the base 110 simply by sandwiching between the base 110 and alid 150. An adhesive 151 may be used to attach the lid 150 to the base.The base 110 may be of any suitable size and shape.

In some embodiments, the first sensor member 120 may include a core 122made of a conductive material, and the cladding 124 which may be made atleast in part of a semiconductor material. In some embodiments, thefirst member 120 may take the form of a fiber including a semiconductormaterial, and in some embodiments the conducting core 122 may be atleast partially surrounded by a semiconducting cladding 124. The fibermay have a circular cross section and include a length substantiallylonger than a transverse dimension (e.g. diameter) thereof.

In the exemplary embodiment shown, the cladding 124 may include anannular shape and may fully surround the core 122 along at least aportion of a length of the core 122. The core 122 may have a shape of acylindrical rod, for example. Both the core 122 and the cladding 124 mayconvey, in operation, electrical current. In some embodiments, the core122 may comprise carbon (e.g. graphite) and the cladding 124 maycomprise silicon carbide (SiC). Silicon carbide/carbon fibers having asuitable SiC cladding and carbon core are manufactured by SpecialtyMaterials Inc. of Lowell, Mass., for example. However, the conductivematerial of the core 122 may also comprise other electrically-conductivematerials including metals such as the noble metals, copper, aluminum,etc. The cladding 124 may comprise other semiconductor materialsincluding Group IV elements such as silicon and germanium, Group IVcompounds such as silicon germanide (SiGe), and Group III-V compoundssuch as gallium arsenide (GaAs) and indium phosphide (InP), amongothers.

In some embodiments, the first sensor member 120 may have a totaldiameter (including the core 122 and cladding 124) of about 150 micronsor less, about 100 microns or less, about 75 microns or less, or evenabout 50 microns or less. In some embodiments, the diameter of the firstsensor member 120 may range between about 75 microns and about 150microns (although larger or smaller sizes may also be used). The core122 may have a diameter between about 10 microns to about 100 microns,or even between about 20 microns to about 40 microns, and may be about30 microns in some embodiments. Other dimensions may also be used.

In the depicted embodiment, the first sensor member 120 may include anend portion with a region of thermally-induced, enhanced electrochemicalactivity 125 (the “enhanced region”). The formation of this region 125is described below more thoroughly. As is illustrated by the plot inFIGS. 11A and 11B, an analyte sensor including the enhanced area on aSiC cladding may increase the response to the analyte (e.g., glucose) bygreater than about five times, or even greater than about 10 times, forexample. Accordingly, a substantially greater response to the analyte isprovided by this aspect of the present invention as compared to a likeSiC member without the enhanced region. In some embodiments describedherein, a current density upon exposure of the sensor to an analyte isgreater than 1 μA/cm², or even greater than 10 μA/cm².

The analyte sensor 100 may further include a second sensor member 130,which in a preferred implementation includes a core 132, which may bemanufactured from a conductive material, and a cladding 134, which mayinclude a semiconductor material. The materials for the second sensormember 130 may be the same as described above for the first sensormember 120. Optionally, the second sensor member 130 may be made of moreconventional materials, such as carbon, graphite, gold, silver,palladium, platinum, etc. For example, the second sensor may be formedof a carbon/graphite PTF. It should be recognized that the referenceelectrode may take on other forms (e.g., a coil, foil, strip, or film).

In some embodiments, however, the second sensor member 130 may be, asshown in FIG. 1, another fiber, which may be oriented in a generallyparallel relationship to the first sensor member 120. Other orientationsmay be provided, such as nonparallel. If the second sensor 130 includesa semiconductor cladding (e.g., SiC), then the sensor member 130 mayinclude a region of thermally-induced, enhanced electrochemical activity127, as described above for the first sensor member 120. The secondsensor member 130 may function as a reference electrode providing areturn path for an electrical current. In one or more embodiments, thesecond sensor member 130 may function as a counter electrode.

Again referring to FIGS. 1-3, applied onto the base 110 and in contactwith, and electrically coupled to, at least the first member 120 is anactive region 140, described below more thoroughly. Briefly, however,the active region 140 may be adapted to be exposed to the bio-fluidsample, and may include one or more catalytic agents or reagents adaptedto promote an electrochemical reaction between an analyte in thebio-fluid sample and the catalytic agents or reagents included in theactive region 140. This may produce reaction products and mobileelectrons, which then may be conducted, for example, by the core 122 orcladding of the first sensor member 120. A mediator, to be describedlater herein, may also be provided in the active region 140 to aid incarrying the electrons to the surface of the core 122 or cladding 124.

According to embodiments of the invention, a cavity 155 may be formedand provided proximate to an open end 135 of the first sensor member120. The cavity 155 (FIG. 2) may receive a bio-fluid sample inserted inthe open end 135 of the sensor 100, for example. In particular, thecavity 155 may be at least partially formed and defined, for example, byinner surfaces of the lid 150 and surfaces of the base 110 (with activeregion 140 applied thereto). The cavity 155 may have any shape, butpreferably has a shape, which promotes capillary action to cause adroplet of bio-fluid to be drawn in and come to rest between therespective regions 125, 127 such that the sample is provided in contactwith the active region 140. A hole 152 may be provided to assist inrelease of displaced air and to promote capillary action.

In some embodiments, a sufficient bio-fluid sample for purposes ofdetecting an analyte concentration level may have a volume of less thanabout 0.5 microliters, less than about 0.4 microliters, or even lessthan about 0.3 microliters, for example. Some exemplary embodiments mayrequire a sample volume to detect an analyte concentration level of lessthan about 0.2 microliters, less than about 0.1 microliters, or evenless than about 0.05 microliters, for example. Other sample volumes mayalso be employed.

Contributing to the need for a lessened volume of the bio-fluid samplemay be the use of the fiber-like shape of the first sensor member 120.This is thought to provide generally-opposed surfaces 141W, 141R(wherein “W” stands for “Working” and “R” stands for “Reference”) forthe active region 140, thus providing a three-dimensional shape, as wellas a relatively large effective surface area of exposed electrode. Assuch, excellent analyte detection may be accomplished with a relativelysmall sample size of the bio-fluid. Moreover, because of the addition ofan enhanced region, a substantially higher signal level may be provided(See FIG. 11). Accordingly, a propensity to have to prick the finger,etc., a second time to obtain sufficient fluid volume for testing may beminimized or avoided.

Referring to FIG. 2, the active region 140 may be positioned within thecavity 155, and is preferably located at a bottom of the cavity 155,thereby allowing exposure of the active region 140 to the samplebio-fluid that enters the cavity 155. As shown, the active region 140 isapplied over, and in contact with, the claddings 124, 134. Inparticular, the active region 140 may be applied over at least a portionof a length of the enhanced regions 125, 127. Upon insertion of thebio-fluid sample into the cavity 155, the cladding 124 and/or core 122may then conduct and channel electron flow and provide an electricalcurrent, which may be proportional to the concentration of the analytein the bio-fluid sample. This current may then be conditioned anddisplayed on a testing apparatus 460 including any suitable readout,such as a digital readout 470 (such as shown in FIG. 4).

As further shown in FIG. 4, an embodiment of an analyte sensor 100 suchas the analyte sensor described with reference to FIGS. 1-3, or any ofthe additional embodiments described herein, may be inserted andreceived into a port 465 of the testing apparatus 460. Electricalcontacts (not shown) in the apparatus 460 come into electrical contactwith conductive ends of sensor members 120, 130 (e.g., the cores and/orcladding thereof) thereby making an electrical connection to thecircuitry of the apparatus 460. Upon applying a voltage bias (e.g.,about 400 mV), conventional processing programs and circuitry may thenequate the current supplied by the sensor 100 to an analyteconcentration level.

Again referring to FIGS. 1-3, one group of catalytic agents useful forproviding the active region 140 is the class of oxidase enzymes whichincludes, for example, glucose oxidase (which converts glucose), lactateoxidase (which converts lactate), and D-aspartate oxidase (whichconverts D-aspartate and D-glutamate). In embodiments in which glucoseis the analyte of interest, glucose dehydrogenase (GDH) may optionallybe used. Pyrolloquinoline quinine (PQQ) or flavin adenine dinucleotide(FAD) dependent may also be used. A more detailed list of oxidaseenzymes which may be employed in the present invention is provided inU.S. Pat. No. 4,721,677, entitled “Implantable Gas-containing Biosensorand Method for Measuring an Analyte such as Glucose” to Clark Jr. whichis hereby incorporated by reference herein in its entirety. Catalyticenzymes other than oxidase enzymes may also be used.

The active region 140 may include one or more layers (not explicitlyshown) in which the catalytic agents (e.g., oxidase enzymes) and/orother reagents may be immobilized or deposited. The one or more layersmay comprise various polymers, for example, including silicone-based ororganic polymers such as polyvinylpyrrolidone, polyvinyl alcohol,polyethylene oxide, cellulosic polymers such as hydroxyethylcellulose orcarboxymethyl cellulose, polyethylenes, polyurethanes, polypropylenes,polyterafluoroethylenes, block co-polymers, sol-gels, etc. A number ofdifferent techniques may be used to immobilize the enzymes in the one ormore layers in the active region 140 including, but not limited to,coupling the enzymes to the lattice of a polymer matrix such as a solgel, cross-linking the agents to a suitable matrix such asglutaraldehyde, electropolymerization, and formation of an array betweenthe enzymes via covalent binding, or the like.

In some embodiments, an electrochemically-active layer (not explicitlyshown) may be positioned adjacent to a working end 135 of the core 122or cladding 124. The electrochemically-active layer may include, forexample, deposited metals, such as a noble metal such as platinum,palladium, gold or rhodium, or other suitable materials. In a glucosedetection embodiment, the active layer may undergo a redox reaction withhydrogen peroxide when polarized appropriately. The redox reactioncauses an electrical current to be generated by electron transfer thatis proportional to the concentration of the analyte that has beenconverted into hydrogen peroxide. This current may be conducted andconveyed from the electrochemically-active layer through the core 122and/or cladding 124 to a testing apparatus 460 as previously describedwith reference to FIG. 4.

In some embodiments, a mediator may be within the active region 140 topromote the conversion of the analyte to detectable reaction products.Mediators comprise substances that act as intermediaries between thecatalytic agent and the working electrode (e.g., the surface of thecore, cladding, an electrochemically active layer applied to the core,or the enhanced region etc.). For example, a mediator may promoteelectron transfer between the reaction center where catalytic breakdownof an analyte takes place and the working electrode, and may enhanceelectrochemical activity at the working electrode. Suitable mediatorsmay include one or more of the following: metal complexes includingferrocene and its derivatives, ferrocyanide, phenothiazine derivatives,osmium complexes, quinines, phthalocyanines, organic dyes as well asother substances. In some embodiments, the mediators may be cross-linkedalong with catalytic agents directly to the working electrode.

To form an electrochemical cell, the second sensor member 130 may becoupled to the active region 140 in the cavity 155. In particular, theactive region 140 may be applied to be in contact with and configured toextend between the claddings 124, 134 having the enhanced regions 125,127 formed thereon. The active region 140 may extend along thegenerally-opposed surfaces 141W, 141R of the claddings 124, 134 as bestshown in FIG. 2, such that a drop of bio-fluid may be received in athree-dimensional feature formed by the active region 140 as appliedover the surfaces of the claddings 124, 134 and base 110.

FIG. 5 is a partially cross-sectioned, partial view of anotherembodiment of an analyte sensor 500 according to the present invention.The sensor 500 comprises a sensor member 520 comprising a semiconductormaterial. The sensor 500 may include a rod-like core 522 of a conductivematerial, and may include a cladding 524 formed at least in part of asemiconductor material. In some embodiments, the member 520 may beprovided in the form of a fiber with the cladding 524 surrounding andencircling the core 522 along at least a portion of the length of thefiber. In this embodiment, the cladding 524 includes a region ofthermally-induced, enhanced electrochemical activity 525.

An active region 540 may be included in contact with at least a portionof the enhanced region 525 of the sensor member 520. The active regionmay be the same as described above. The active region 540 applied to theregion of thermally-induced, enhanced electrochemical activity 525 mayenhance the electrochemical activity and analyte response as will bedescribed below in more detail. The analyte sensor 500 may be includedwithin another structure or device, such as within a cavity or within ahollow member.

Additionally, in the depicted embodiment of FIG. 6, a sensor member 620of an analyte sensor 600 may be provided with an annulus or annuli,which constitute one or more regions of thermally-induced, alteredconductivity 625A-625C. In particular, the enhanced regions 625A-625Cmay provide for the application of information coding, for example. Thecoding may allow certain information to be coded onto the sensor member620. The coded information may relate to the properties and/or featuresof the sensor 600, for example. In particular, a date of manufacture,lot number, part number or version number, calibration data orconstants, expiration date, or the like may be encoded. This codedinformation may be read by the testing apparatus (e.g., apparatus 460shown in FIG. 4) upon insertion of the sensor 600 in the apparatus.

As best shown in enlarged view in FIG. 6, and in the case where asemiconductor cladding material is used (e.g., SiC), the regions ofthermally-induced, altered conductivity 625A-625C may be formed of, andinclude, one or more altered conductivity tracks (e.g., rings). Thetracks may be formed on the cladding 624 of the sensor member 620, andmay extend inwardly in a radial direction to the core 622. In thedepicted embodiment, three altered conductivity tracks 625A-625C areshown. However a greater or lesser number of tracks may be used. Forexample, in one embodiment, a single track of variable width may beused, wherein a two-point measurement of resistance may be taken tomeasure and determine a level of resistance. That resistance value maythen be correlated to a code in a look-up table, for example. Theresistance level may be varied by adjusting the power and/or sweepconditions employed when forming the track, for example.

In the depicted embodiment of FIG. 6, the plurality of spaced, alteredconductivity tracks may be provided on the sensor member 620. The trackspositioned on the member 620 may be used to provide bits of codedinformation (e.g., 1's and 0's) which thereafter may be read from themember 620 by a suitable reader provided in a testing apparatus (SeeFIG. 4)). For example, a track existing at a defined location spacedfrom a terminal end of the sensor 600 may be used to signify a “1,”while the absence of a track at a defined location (see location 691)may indicate a “0.” Accordingly, with only 4 predetermined tracklocations, 2⁴ bits or 16 codes may be provided which then may be read bya testing apparatus (not shown), for example. The testing apparatus mayinclude electrical contacts (not shown) which contact at each spacedlocation where a track may be placed, and may read out a resistancevalue to determine the bits (1 or 0) at each location. In someembodiments, it may be desirable to code information on other sensormembers, if provided.

As best shown in FIG. 7, a method of forming one or more regions ofthermally-induced, altered conductivity 625A-625C is provided. Each ofthe regions 625A-625C may be formed, for example, by subjecting the SiCcladding 624 of the sensor member 620 to intense localized heat at asuitable temperature. The surface temperature provided should besufficient to provide a suitable alteration in the conductivity of aregion relative to the nonprocessed regions. In the case of formation ofthe enhanced activity region, a suitable temperature may be employed toprovide a suitable alteration in electrochemical activity relative tothe nonprocessed regions. A suitable surface temperature for formationof the regions may be greater than about 1,000° C., greater than about1,500° C., or even greater than about 2,000° C., for example.

For example, the cladding 624 may be exposed to a laser beam 796 emittedfrom a laser 797 as the member 620 or laser 797 are subjected toperpendicular motion relative to the other (designated by arrow 728).The fiber may then be rotated or flipped over 180 degrees and the sameprocess repeated on the other side. In some cases, it may be moreefficient to process many fibers in a side by side orientationsubjecting them all to a common laser treatment.

The laser 797 may be any suitable laser, having suitable power toeffectuate an appropriate thermal change in the fiber. One suitablelaser may be a yttrium vanadate laser (“Y-V0₄ laser”) having a power ofbetween about 5 and 250 watts and providing a beam width of betweenabout 30 microns and about 250 microns, for example. The wavelengthsused can be the natural wavelength of about 1064 nm, the frequencydoubled wavelength (about 532 nm) or frequency tripled wavelength (about355 nm). The scanning movement of the member 620 may be such that asurface rate of the laser beam 796 in the perpendicular direction may beat a scan rate of between about 20 mm/s and 2000 mm/s, and in someembodiments about 200 mm/s. In the case where large areas of the membersare being treated, the laser 797 may scan in the Y direction and then bespaced incrementally along a longitudinal length (X direction) of themember 620 by a small increment and the scan repeated in the Ydirection. The increment may be small enough such that the affectedregions abut or overlap slightly. The laser may scan a plurality ofparallel aligned fibers at once, in both X and Y directions, that is thescan may cover a square or rectangular field and marks the entiredesired pattern without moving the fibers. The fibers may be flippedover to treat the previously hidden underside. This sequence of scanningand spacing may be repeated until a region of the desire length isformed. The laser may be pulsed at a frequency of between about 10 kHzand about 100 KHz. Other high-powered lasers may be used, such as YAG,C0₂, excimer, laser diodes, slab, thin disc, fiber, and green lasers.

The intense localized heating of the cladding 624 comprised ofsemiconductor material (e.g., SiC) may cause a localized alteration inresistivity and/or electrochemical activity of the cladding 624. Assuch, the localized heating may provide an altered conductivity track ortracks 625A-625C encircling the core 622 (shown dotted). In someembodiments, the region may penetrate radially into the member to adepth sufficient to reach the core 622. Upon exposure to sufficientheat, the tracks 625A-625C may have a conductivity, which may be severalorders of magnitude, or more different from a surrounding SiC materialnot subjected to the heat from the laser application. Further, in thecase where an enhanced region is formed, such as in the embodiments ofFIG. 1-3, FIGS. 5, 8A-8D, and 14, for example, the method describedabove may be used.

In accordance with another aspect, a fill detector function may beprovided proximate to the active region to ensure that a sufficientbio-fluid sample is present when performing a detection of an analyteconcentration. For example, a fill detector function may be provided byproducing a conductive track (like track 625C) on each of two sensormembers (a first sensor member and a second sensor member) at a positionproximate the active region. For example, the fill detector track may beprovided an equal distance from the active region on each sensor member.The tracks may be formed as described above.

In operation, if a sufficient bio-fluid sample is present, a portion ofa bio-fluid sample will come to rest between the fill detector tracksformed on the sensor members and provide a conductive path through thebio-fluid sample. Accordingly, when the bio-fluid is present at thelocation of the fill detector tracks, then a significant lowering ofelectrical resistance between the sensor members may be measured.

FIGS. 8A-8D illustrate various embodiments of sensor members 820A-820D,respectively, according to the present invention. In the firstembodiment of FIG. 8A, the sensor member 820A may be formed as a fiberincluding a semiconductor material (e.g., a cladding of SiC) and mayinclude a region of enhanced electrochemical activity 825 only on an endportion of the semiconducting member 820A. This region 825 may be formedon a surface region of a semiconducting portion of the semiconductingmember, and may be thermally induced as described above, for example.Optionally, the enhanced region 825 may be formed elsewhere on themember, such as in the middle (FIG. 8C), or at severallongitudinally-spaced locations (FIG. 8D). In these embodiments, theenhanced region 825 may be provided on less than all of a peripheralradial surface of the member 820C, 820D, respectively. The region(s) 825may be provided as an annulus or a plurality of annuli, for example. Anactive region, such as region 540, as described in the FIG. 5embodiment, may be applied to at least a portion of the enhanced regions825 to form an analyte sensor in each case.

In the FIG. 8B embodiment, an entire radial peripheral surface of themember 820B may be provided with a surface region enhancedelectrochemical activity 825. In the depicted embodiments, heat (e.g.,via a laser beam) may be applied such that the region 825 may bethermally induced on an outer surface of the sensor member 820A-820D.The region 825 may include a radial depth (d), measured from a surface(e.g., a radial peripheral surface) inwardly, of at least 5 microns (seeFIG. 8A). In some embodiments, the depth (d) of the region 825 may be atleast 10 microns, or even at least 20 microns. In some embodiments, theregion 825 may extend to a conductive core of the member 820A-820D.

FIGS. 9A-9D illustrate micrographs at various magnifications, with andwithout a region of thermally-induced, enhanced electrochemical activity825B provided on a surface of the member. In particular, FIGS. 9A and 9Billustrate surface regions of a semiconducting member (e.g., asemiconducting fiber) at 10,000× magnification, with and without,respectively, a thermal surface treatment (e.g., heating with a laser)providing an enhanced region. FIG. 9A illustrates clearly a change insurface morphology wherein generally spherically-shaped globules 950 areformed on the surface. The globules 950 may vary in cross-sectionalmaximum dimension from about 100 nanometers to about 5 microns, forexample. It is believed that the globules may increase the effectivesurface area or the effective surface conductivity, or both. In anyevent, it has been discovered that applying heat to a surface region ofthe semiconducting member may bring about a change in an electrochemicalactivity of at least the surface region. FIG. 9B illustrates alike-sized region of the member as compared to the region of FIG. 9Awithout the application of heat to the surface (an unenhanced region).FIGS. 9C and 9D illustrate further micrographs at 500× magnificationillustrating a thermally-induced, enhanced activity surface in FIG. 9Cas compared to an unenhanced surface of FIG. 9D at the samemagnification.

FIG. 10 illustrates an embodiment of a member 1020, which may be asemiconducting fiber and wherein a surface of the semiconductingcladding of the fiber has formed thereon a surface region of enhancedelectrochemical activity 1025, which may be thermally induced. As shown,the enhanced region 1025 may be provided on less than all of a surfaceof the sensor member 1020. As described before, an active region 1040may be applied to at least a portion of the enhanced region 1025 therebyforming an analyte sensor.

FIG. 11A illustrates a plot of a electrical response (in nanoamperes(nA)) of a sensor member including a region of enhanced electrochemicalactivity of the present invention (labeled 1101A) as against a sensormember having no enhanced region (labeled 1102A) upon exposure tovarious levels of glucose analyte containing control solution. Thesensor members were each fibers having an outer silicon carbide claddingof an outer diameter of about 140 microns and a carbon core having adiameter of about 30 microns. The sensor member including an enhancedregion was subjected to heating from a YAG laser set at a power of about50 watts and pulsed at about 100 kHz. The laser beam width was about 65microns and the fibers were ablated by scanning the laser numerous timesacross the surface of the fibers at a scan rate of about 200 mm/s and asuitable spacing. Numerous fibers were laid side by side on a flatsurface of an anodized backing plate and the laser scan was performedacross the width of the collection of fibers. The laser was then spacedalong the longitudinal length of the fibers by a small increment (about0.025 mm) and the scan repeated to produce an exposed region about s 5mm long. The fibers were then flipped over and the process repeated. Theapplication of heat by the laser provided a region of enhancedelectrochemical activity, which was thermally induced. The other sensormember was left untreated (unenhanced).

Each member then had applied thereto a same active region made of 0.9 gferricyanide, 0.3 g HEC and 0.3 g GOx in a 14.4 g of a 7.4 pH buffersolution by dipping. In the treated fiber, the active region was appliedon top of the region of enhanced electrochemical activity. The core ofthe fibers in this test were sealed to evaluate the effect of thesemiconductor cladding. In the test, each sensor member was subjected toan analyte solution containing various concentrations of a glucosecontrol solution from about 4 to about 62 mg/dL. As is demonstrated fromthe plot, an electrochemical response of the sensor member having anenhanced activity region was greater than about 5 times, or even greaterthan about 10 times for a 60 mg/dL concentration of glucose solution.Accordingly, analyte sensors including the electrochemically enhancedregion of the invention may have a substantially increasedelectrochemical response (current density) to an analyte (e.g., glucose)as compared to a like untreated fiber.

FIG. 11B demonstrates another comparison of untreated and treated fibersas described above with reference to FIG. 11A, however, in this test,the carbon core was left unsealed in each fiber. The same preparationconditions were used as in the FIG. 11A test, except for the cores beingleft unsealed. In this test, the treated fiber 1101B having a region ofenhanced electrochemical activity formed by laser treatment also showsan increase in response of greater than about 5 times, or even greaterthan about 10 times as compared to the unprocessed fiber 1102B. Thesetests may indicate that the enhancement is coming from the heattreatment received by of the SiC cladding of the fiber.

A method for manufacturing embodiments of devices with regions ofenhanced electrochemical activity surfaces according to aspects of theinvention will now be described with reference to FIG. 12. The method1200 may include steps of providing a member (e.g., a sensor member)including semiconductor material as in step 1202, and then applying heatto a surface region of the member as in step 1204 for a time, and at atemperature, sufficient to form a surface region of enhancedelectrochemical activity on a semiconductor portion of the member. Thetreatment may be sufficient to bring about a change in electrochemicalactivity of greater than 2 times, greater than 5 times, or even greaterthan 10 times, as compared to an untreated member.

The member may be a sensor member formed from a fiber having a lengthsubstantially longer than its width and the fiber may include asemiconductor material, such as a cladding of SiC, for example. The heatmay be applied as discussed above, such as by a high-power laser to atemperature in excess of 1,000° C., 1,500° C., or even 2,000° C., forexample. The thus-formed electrochemically enhanced region may encompassall, or less than all, of a surface (e.g., some of a radial surface, oronly one side) of the member.

In the case of the member being used in an analyte sensor, following thestep of applying heat, an active region may be formed on at least aportion of the surface region of enhanced electrochemical activity as instep 1206. The step of applying the active region may be by anyconventional process for applying such catalysts and/or reagents asdescribed above.

FIG. 13 illustrates an embodiment of an electrochemically active device1300, which may be manufactured from a semiconducting material (e.g.,silicon carbide). The device 1300 may, like the members described above,include a surface region of enhanced electrochemical activity 1325,which may be thermally induced. The region 1325 may extend into thedevice by a depth (d) which may be less than a total thickness of thedevice 1300. In some embodiments, the device 1300 may be formed from abody of porous semiconducting material (e.g., a body of semiconductingporous foam). The porous foam semiconductor material may be SiC and mayinclude a density of less than about 20%, and even between 4% and 12%,for example. As shown, the member 1300 may be formed as a panel having athickness much less than a length or width dimension. In particular, thedevice 1300 may find utility as a porous electrode for anelectrochemical conversion device used in an electrochemical process,such as a fuel cell or battery, for example.

A surface of the device 1300 may be made substantially moreelectrochemically active by subjecting a surface of the panel to heat,such as by performing a raster scan of a laser beam 1396 emanating froma laser 1397 (e.g., a YAG laser) in a path 1398 across the surface 1399of a porous semiconducting foam panel, for example. A suitable rasterscan may include repeated passes across the face of the panel, spaced atappropriate intervals such that substantially all the surface 1399 maybe provided with enhanced electrochemical activity. As described above,the surface 1399 may be heated by a sufficient amount (e.g., greaterthan 1,000° C., greater than 1,500° C., greater than 2,000° C.) to bringabout a suitable change in activity (e.g., greater than about 2 times,greater than about 5 times, or greater than about 10 times as comparedto an untreated device).

FIG. 14 illustrates another exemplary embodiment of an analyte sensor1400. The analyte sensor 1400 may include a first and second sensormember 1420, 1430, respectively aligned next to each other in a parallelorientation. The members 1420, 1430 may be semiconducting fibers as weredescribed with reference to FIG. 5 and may be received within andsecured in an annular sleeve 1414, which may be made of an insulatingmaterial, for example. Each of the sensor members 1420, 1430 may includea region of enhanced electrochemical activity 1425 which may bethermally induced (as described herein) and may include an active region1440 applied over the enhanced regions 1425 which forms a bridge ofmaterial between the members 14290, 1430 at the end thereof. Of course,the first and second sensor member 1420, 1430 are otherwise electricallyinsulted from one another along their length. The insulation may beprovided by a potting compound or a suitably thin layer of polymerinsulation for example, such as a polypropylene layer, polycarbonate,polytetrafluorethylene or the like. The assembly including the members1420, 1430 and sleeve 1414 may be received in a hollow member 1402,which may include a cleaved end forming a lancet. The hollow member 1402may be made of a suitable rigid material, such as stainless steeltubing.

The analyte sensor 1400 provides a combined lancet and sensor apparatus,which eliminates the need to have a separate lancet as well as a usertransfer of a bio-fluid to a test strip. The analyte sensor may furtherinclude a coded region 1450, which may include one or more tracks aswere described with reference to FIGS. 6 and 7.

The foregoing description discloses only exemplary embodiments ofdevices, members, sensors, analyte sensors, apparatus including thesame, and methods of manufacturing the sensors and devices of theinvention. Modifications of the above disclosed devices, members,sensors, analyte sensors, apparatus including the same, and methods ofmanufacturing the sensors and devices, which fall within the scope ofthe invention, will be readily apparent to those of ordinary skill inthe art.

Accordingly, while the present invention has been disclosed inconnection with exemplary embodiments thereof, it should be understoodthat other embodiments may fall within the spirit and scope of theinvention, as defined by the following claims.

The invention claimed is:
 1. A method of manufacturing an analyte sensorfor measuring glucose concentration in a bio-fluid, the methodcomprising: providing a sensor member in the form of a fiber including acore formed of conductive material surrounded by a cladding formed of asemiconductor material including silicon carbide; providing a surfaceregion of enhanced electrochemical activity on the cladding of thesensor member by applying heat via laser to a portion of a surface ofthe sensor member sufficient to alter a response to an analyte of thecladding exposed to the heat to be five or more times greater thanbefore exposure; and providing an active region over at least a portionof the surface region of enhanced electrochemical activity, the activeregion including an agent selected from among glucose oxidase, glucosedehydrogenase (GDH), pyrolloquinoline quinine (PQQ), and flavin adenine25 dinucleotide (FAD), and being adapted to be exposed to a bio-fluidsample.
 2. The method of claim 1 wherein the laser is pulsed at betweenabout 10 kHz and about 100 kHz.
 3. The method of claim 1 wherein thelaser is moved along a dimension of the sensor member at a rate ofbetween about 20 mm/s and about 200 mm/s.
 4. The method of claim 1wherein the surface region constitutes less than all of an entiresurface of the sensor member.
 5. The method of claim 1 wherein thesurface region constitutes substantially all of a peripheral surface ofthe sensor member.
 6. The method of claim 1 wherein the surface regionof enhanced electrochemical activity extends inwardly from the surfaceof the sensor member to a depth of at least 5 microns.
 7. The method ofclaim 6 wherein the depth is at least 10 microns.
 8. The method of claim1 wherein the surface region of enhanced electrochemical activity isthermally induced by subjecting the surface region to a temperature ofgreater than about 1000° C. without removing a significant amount ofmaterial from the surface region.
 9. The method of claim 8 wherein thetemperature is greater than about 1500° C.
 10. The method of claim 8wherein the temperature is greater than about 2000° C.
 11. A method ofmanufacturing an analyte sensor for measuring lactate concentration in abio-fluid, the method comprising: providing a sensor member in the formof a fiber including a core formed of conductive material surrounded bya cladding formed of a semiconductor material, the semiconductormaterial including one of silicon, germanium, silicon germanide (SiGe),gallium arsenide (GaAs), and indium phosphide (InP); providing a surfaceregion of enhanced electrochemical activity on the cladding of thesensor member by applying heat via laser to a portion of a surface ofthe sensor member sufficient to alter a response to an analyte of thecladding exposed to the heat to be five or more times greater thanbefore exposure; and providing an active region over at least a portionof the surface region of enhanced electrochemical activity, the activeregion including lactate oxidase and being adapted to be exposed to abio-fluid sample.
 12. The method of claim 11 wherein the surface regionconstitutes less than all of an entire surface of the sensor member. 13.The method of claim 11 wherein the surface region of enhancedelectrochemical activity is thermally induced by subjecting the surfaceregion to a temperature of greater than about 1000° C. and wherein thecladding is formed from SiC.
 14. A method of manufacturing an analytesensor for measuring an analyte concentration in a bio-fluid, the methodcomprising: providing a rod-shaped conductive core; forming an annularcladding of a semiconductor material surrounding the core, thesemiconductor material including one of silicon, germanium, silicongermanide (SiGe), gallium arsenide (GaAs), and indium phosphide (InP);forming a surface region of enhanced electrochemical activity on thecladding by applying localized heat via laser to a portion of a surfacearea of the cladding sufficient to alter a response to an analyte of thecladding under the surface area exposed to the localized heat to be fiveor more times greater than before exposure; and forming an active regionover at least a portion of the surface region of enhancedelectrochemical activity, the active region including D-aspartateoxidase and being adapted to be exposed to a bio-fluid sample.
 15. Themethod of claim 14 wherein the surface region is less than all of anentire surface of the cladding.
 16. The method of claim 14 wherein thesurface region of enhanced electrochemical activity is thermally inducedby subjecting the surface region to a temperature of greater than about1000° C. and wherein the cladding is formed from SiC.
 17. The method ofclaim 16 wherein the temperature is greater than about 1500° C.